Amyotrophic Lateral Sclerosis (ALS) is a fatal progressive motor neuron degeneration disease. Current treatment options are inadequate and only minimally improve quality of life and survival times. There is an acute need for novel treatments that prolong lifespans of ALS patients and improve their quality of life. Xenon (Xe) gas has been used clinically as an anesthetic, it is considered safe and induces few side effects, and data exist suggesting that it may be therapeutically useful via several mechanisms for counteracting neurodegenerative processes. Accordingly, we propose an initial pilot study to assess xenon efficacy for delaying onset of motor impairments and reducing apoptosis and glial activation in the C57Bl/6 SOD1G93A model of familial ALS. We hypothesize that continuous Xe inhalational exposure will delay development of motor impairments and reduce apoptosis and glial activation in C57Bl/6 SOD1G93A mice. Should we validate our hypotheses, this will set the stage for systematic investigations to optimize Xe exposure conditions in the C57Bl/6 SOD1G93A model, which could ultimately lead to the clinical use of Xe to treat ALS. PUBLIC HEALTH RELEVANCE: Amyotrophic lateral sclerosis (ALS) is a chronic progressive neurodegenerative disorder with major public health implications. Xenon gas has been used clinically as an anesthetic and it may be useful for slowing ALS- associated neurodegeneration. This project aims to initially test whether xenon can slow or prevent the development of motor system dysfunction and markers of apoptosis and glial activation in the C57Bl/6 SOD1G93A mouse model of familial ALS.